SURVIVAL FACTORS REQUIRED BY VISUAL SYSTEM NEURONS. Very little information is available to illuminate the specific cellular and molecular interactions required for the development of the brain and spinal cord. The major objective of the proposed studies is to identify the specific neurotrophic molecules required for the survival of identified groups of neurons in the developing vertebrate visual system. These studies will investigate the effects of brain derived neurotrophic factor (BDNF), a rare protein recently isolated from the brain. It is capable of supporting the survival of select groups of neurons in vitro, including rat retinal ganglion cells. Experiments will test the hypothesis that BDNF is a target-derived survival molecule which is normally required by retinal ganglion cells during critical periods of development. The effects of BDNF will be investigated using retinal ganglion cells isolated in vitro as well as studies in which embryos are treated with the factor during the normal development of the visual system. In addition, this project will focus on a second putative neurotrophic factor also derived from the brain. The ability of purified factors to support neuronal survival will be investigated with identified cells isolated from the retina, superior colliculus and visual cortex. Survival molecules which are identified as important physiological requirements for the development of the CNS may also play an important role in the mature function, plasticity, regeneration, transplantation and aging of CNS tissues. The proposed investigations of the molecular events which determine the development of visual system neurons may also form a basis and provide molecular tools for similar studies in other regions of the CNS.